Recent advances in mammalian genome studies are bringing to light the occurrence of a widespread transcription of non-coding (nc) regions devoted to the regulation of the protein coding genome expression [1-4]. The mechanisms of action of these transcripts are various and of different nature, although all of them are devoted to the regulation of fundamental genetic pathways involved in the determination of the cell phenotype. The concomitant evolution of non-coding regulatory transcripts and proteins that target different RNA:RNA or RNA:DNA complexes emphasizes the importance to study the regulatory processes mediated by nucleic acids interactions. It's now clear that either in procaryotes as well as in eukaryotes different ncRNAs can act in cis and be contemporaneously regulated in trans by other non-coding transcripts. The simultaneous occurrence of cis and trans regulatory elements bring to light the complexity of this network where the coexistence of different non-coding RNAs plays a key role in the control of other targets gene expression [5]. In this context a prominent role is played by the enlarging family of microRNAs (miRNAs) that act at post transcriptional level by inhibiting the translation of protein coding genes [6]. The known miRNAs, as protein-coding mRNAs, are synthesized as polyadenylated precursor molecules by the RNA Polymerase II transcription machinery [7]. Considering that the vast majority of the tools used in molecular biology are based on transcript collections obtained by oligo-dT RT-PCR (thus encompassing only polyadenylated RNA Polymerase II products) a wide contribution of non-polyadenylated transcripts to the human transcriptome has been shown [8]. However, the role of such transcripts in Pol II transcriptome expression regulation remains largely unexplored.
Among the non-coding elements one of the most investigated has been the Alu class of repetitive sequences that represents about one tenth of the whole human genome. Although it is not yet possible to discern a peculiar Alu's role these short transcripts has been shown to be involved in several biological processes such as RNA editing (where Alus are preferential sites for A to I RNA editing thus having profound implications either in gene expression regulation as well as in the mammalian genome evolution) [9], alternative splicing (internal exons that contain an Alu sequence are almost always alternatively spliced) [10], chromosomal recombination (the recombination between Alu elements is at the base of many genomic deletions associated with many human genetic disorders) [11], gene expression regulation (functioning as naturally occurring antisense RNAs) [12], cell stress response (such as heat shock response and/or translation inhibition) [13] and as putative miRNAs targets [14]. However, although the physiological role of Alus and all the other 7SL-derived transcripts needs to be further studied in detail, the fact that their transcription is RNA Polymerase (Pol) III-dependent bring to light a previously unexpected role in gene expression regulation of this enzyme that would need to be investigated in detail.
In this work we focus on a specific class of non-coding RNAs starting from a theoretical hypothesis on their putative function. In fact, starting from the observation that RNA Polymerase (Pol) III is specialized in transcription of non coding ncRNA genes, we postulated the presence in the genome of a large number of Pol III (or Pol III-like) transcription units each specifically regulating one (or more) specific Pol II genes, thus constituting functional “co-gene”/gene pairs.